To complement biochemical and fluorescence light microscopy studies on papillomavirus infection and virion assembly being conducted by NCI investigators, we are determining the high-resolution distribution of the papillomavirus capsid protein L2 within infected epithelial cells grown in culture. Infected cells were pelleted, high-pressure frozen, freeze-substituted, plastic embedded and sectioned. Some sections were stained and imaged at a beam voltage of 120 kV in an energy-filtering transmission electron microscope to characterize the cellular ultrastructure, while other sections were immunolabeled with gold-conjugated antibodies against the L2 virion protein. Experiments are in progress to localize the capsid proteins within the infected cells, particularly in specific regions of the nucleus.